In eukaryotic cells, many signaling pathways use phosphodiesterases, which degrade the second messengers cAMP and cGMP. PDEs (3',5' cyclic nucleotide phosphodiesterases) degrade cGMP or cAMP to the 5' monophosphate nucleotide. To date, no structure for any PDE has been reported. An active, 36 kD proteolytic fragment of PDE2A1 (calmodulin-stimulated PDE) from bovine brain has been crystallized. This active fragment contains the entire ~250 residue catalytic consensus sequence found among the 9 PDE families. The cubic I23 crystals are grown with the nonspecific PDE inhibitor IBMX (3-isobutyl-1-methylxanthine). Diffraction to 4 E has been observed in-house.